BackgroundHIV/AIDS persists as a global health challenge despite significant advancements in antiretroviral therapy (ART). The transformation of HIV into a chronic condition, coupled with regional disparities and evolving epidemiological trends, necessitates an updated analysis of the disease burden.MethodsWe conducted a comprehensive analysis of HIV/AIDS burden among individuals aged 15-79 years from 1990 to 2021 using the latest data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 database. Multiple statistical approaches were employed to investigate temporal trends, geographic variations, and health inequalities.ResultsFrom 1990 to 2021, global HIV/AIDS age-standardized incidence rates (ASIR) decreased by 41%, while age-standardized prevalence rates (ASPR), mortality rates (ASMR), and disability-adjusted life year rates increased by 222%, 57%, and 59%, respectively. Sub-Saharan Africa demonstrated the highest HIV/AIDS ASPR in 2021, with High-middle and Middle SDI regions, particularly Oceania, South Asia, and Eastern Europe, experiencing the most significant ASPR growth over three decades. Joinpoint analysis identified 1997 and 2015 as critical years for ASIR declines, and 2004 for ASMR reductions. Decomposition analysis revealed population growth as the primary driver of increasing incidence in lower SDI regions, while epidemiological changes were more influential in higher SDI areas. The age-period-cohort model showed peak HIV/AIDS incidence among individuals aged 25-34, with diminishing incidence risk across successive birth cohorts and periods. Health inequality analysis from 1990 to 2021 revealed a substantial widening of disparities across countries, with the slope index of inequality rising from 265 to 1006.ConclusionWhile global efforts have reduced HIV/AIDS incidence, increasing prevalence due to extended survival with antiretroviral therapy presents ongoing challenges. Regional disparities and rising incidence among specific demographics underscore the need for sustained, targeted interventions.